Ketoconazole Dosage

Usual Adult Dose for Oral Thrush

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for 1-2 weeks.

Usual Adult Dose for Dermatophytosis

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for 4 weeks.

Usual Adult Dose for Blastomycosis

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for at least 6 months.

Usual Adult Dose for Coccidioidomycosis

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for at least 6 months.

Usual Adult Dose for Histoplasmosis

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for at least 6 months.

Usual Adult Dose for Paracoccidioidomycosis

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for at least 6 months.

Usual Adult Dose for Chronic Mucocutaneous Candidiasis

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for 3-12 months. Patients usually require maintenance therapy.

Usual Adult Dose for Esophageal Candidiasis

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for 2-3 weeks.

Usual Adult Dose for Onychomycosis - Fingernail

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for 6-12 months.

Usual Adult Dose for Onychomycosis - Toenail

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for 6-12 months.

Usual Adult Dose for Vaginal Candidiasis

Initial dose: 200 mg orally once a day.
May be increased to 400 mg once a day for more severe or resistant infections. Treatment should be continued for approximately 1 to 2 weeks and until tests indicate the resolution of the infection.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

Ketoconazole may cause hepatotoxicity, primarily of the hepatocellular type. Patients receiving this drug should be made aware by the prescriber of the risk and should be closely monitored. The median duration of ketoconazole therapy in patients who developed symptomatic hepatotoxicity was about 28 days, although the range extended to as low as 3 days. The hepatic injury has usually, but not always, been reversible after discontinuing the drug. Prompt recognition of liver injury is vital. Baseline and periodic liver function tests (such as SGGT, alkaline phosphatase, SGPT, SGOT and bilirubin) are recommended. Patients receiving prolonged therapy with ketoconazole or concomitant therapy with other hepatotoxic agents, as well as those with a history of liver disease, should be monitored carefully. Most of the cases of hepatic toxicity to date have been treated for onychomycosis. Transient minor elevations in liver enzymes have been reported during treatment with ketoconazole tablets. Ketoconazole should be discontinued if these persist, if the abnormalities worsen, or if the abnormalities become accompanied by symptoms of possible liver injury.

Concomitant administration of terfenadine with ketoconazole tablets is contraindicated. Rare cases of serious cardiovascular (CV) adverse events, including death, ventricular tachycardia and torsades de pointes have been observed in patients taking ketoconazole tablets concomitantly with terfenadine, due to increased terfenadine concentrations induced by ketoconazole tablets. Pharmacokinetic studies indicate that oral ketoconazole inhibits the metabolism of astemizole, resulting in elevated plasma levels of astemizole and its active metabolite desmethylastemizole which may prolong QT intervals. Concomitant administration of astemizole with ketoconazole is therefore contraindicated. Coadministration of ketoconazole with cisapride is contraindicated since serious CV adverse events including ventricular tachycardia, ventricular fibrillation and torsades de pointes have been reported. Coadministration of ketoconazole tablets with oral triazolam is contraindicated.

Several cases of hypersensitivity reactions including urticaria have also been observed. Increased fragility of long bones, in some cases leading to fracture, have been observed in female rats treated three to six months with ketoconazole at dose levels of 80 mg/kg and higher. The maximum "no-effect" dose level in these studies was 20 mg/kg (2.5 times the maximum recommended human dosage). The mechanism responsible for this phenomenon is unclear. Limited studies in dogs failed to demonstrate such an effect on the metacarpals and ribs.

Ketoconazole tablets have been reported to lover serum testosterone. Once treatment with ketoconazole tablets has been discontinued, serum testosterone levels return to baseline values. Levels of testosterone are impaired with doses of 800 mg per day and abolished by 1600 mg per day. ACTH corticosteroids serum levels are decreased with ketoconazole tablets at similar high doses. The recommended dose of 200 mg to 400 mg daily should be monitored closely.

In four subjects with drug-induced achlorhydria, a marked reduction in ketoconazole absorption was reported. Ketoconazole tablets require acidity for dissolution. If the patient has achlorhydria, they should be instructed to dissolve each tablet in 4 mL aqueous solution of 0.2 N HCL. For ingesting the resulting mixture, the patient should use a drinking straw so as to avoid contact with the teeth. A cup of tap water should follow the administration.

Many HIV patients have hypochlorhydria, which may impair the absorption of ketoconazole and cause treatment failure. For these patients, an alternative antifungal agent may be appropriate.

In many patients with hematological malignancies, unpredictable and often lower serum concentrations of ketoconazole have been reported. For these patients, an alternative antifungal should be considered.

Dialysis

Ketoconazole is not dialyzable (0%-5%).

Other Comments

There should be laboratory as well as clinical documentation of infection prior to starting ketoconazole therapy. Treatment should be continued until tests indicate that active fungal infection has subsided.

See also...